KR0171549B1 - Solid state sensors - Google Patents

Abstract

The present invention is formed from a polymer that is inert to the medium and analyte and does not affect the sensitivity of the indicator, wherein the polymer is a crosslinked solid silicone rubber formed from silicone carbinol having a molecular structure compatible with the indicator. It relates to a stabilized bio-inert sensor for the determination of analytes, in particular pO ₂ , pCO ₂ and pH, in a medium comprising chemical indicators sensitive to the analyte while stabilizing the substrate.

Description

Solid state sensors

Measurements of pO ₂ , pCO ₂ and pH of blood during surgical operations, post-surgery and during hospitalizations under intensive care are important, and various sensor instruments for the measurement of these parameters and for various monitoring are disclosed in the art. For determining the concentration of an analyte in a liquid medium, a sensor instrument, referred to herein as a sensor, typically varies in the presence of an analyte with a suitable carrier or substrate that also acts as a transmission line that shifts the signal indicating a change to a suitable detector. It consists of a detector with features. For example, the use of pyrenbutyric acid as a fluorescence detector to determine the oxygen concentration in the blood is known and used in such sensors with optical fibers, in which the fluorescence detector closed with a selective permeable membrane is described in US Pat. No. 4,476,870. Is disclosed.

Sensors using fluorescence detectors and having satisfactory functions in the biological environment should have four characteristics: sensitivity, short reaction time, stability and bio-inertness.

The sensitivity depends on the quantum efficiency of the fluorescent indicator, the concentration of the indicator present in the sensor and the availability of the indicator for the substrate, i. Thus, sufficient amount of indicator must be available to produce a meaningful fluorescence reaction. However, if the indicator molecules are placed too close to each other, a type of behavior often occurs that is detrimental to the operation of the sensor; This behavior is known as excimer fluorescence. Thus, a given indicator has an optimal indicator concentration for maximum sensitivity.

Another problem that must be solved in the construction of a fluorescent sensor is the availability of the indicator in the sensed environment. If the ion or gas of interest does not reach the indicator molecule, the indicator will not respond to the presence or absence of the ion or gas. This problem is clearly related to the permeability of the structure containing the indicator molecule.

Reaction time is also associated with permeability. If the sensed substrate (ie ions or gases) is dispersed very slowly through the structure, the sensor's response time will be relatively long, which greatly reduces its usefulness.

Sensors that measure blood gas or blood pH should be available for hours or days. Recalibration of sensors in use in vivo is sparse, inefficient or even impossible. Thus, the stability of the sensor is a decisive factor in determining its usefulness. A common problem in fluorescence sensor designs is the progressive loss of indicator from the sensor. This lowers the sensitivity, which makes the display of the sensor unstable, even at constant concentrations, and liberates chemical indicators in the blood flow. Instruments that release chemical indicators into the blood flow cannot be considered bioinert. Bio-inert, as used herein, refers to the characteristics of an instrument, i.e., a sensor, in which any and all chemicals that are part of the instrument are firmly fixed to the structure of the instrument so that it is not liberated or exuded from the instrument under routine operating conditions.

The problem of exuding indicator material from a sensor in the prior art, which is inherent when small molecules are embedded in a polymerizable matrix, has generally approached the indicator to be wrapped or embedded in a selectively permeable membrane.

In practice, the problem is evident by the gradual loss of sensitivity as the indicator is lost; This requires a combustible recalibration of the sensor.

The above mentioned prior art arrangement does not completely solve the problem since some of the indicator material is still exuded from the sensor. Thus, the problem of recalibration remains, and moreover, the free indicator flows into the patient's blood flow.

Thus, there is a need to provide a more stable sensor in which the indicator does not exudate or flush out of the sensor when in contact with the fluid of the body.

The desired stability is in accordance with US Pat. No. 5,019,350, wherein the optical fiber has a distal end that is stably bound to an adhesive water-insoluble organic polymer having a plurality of fluorescent organic substituents, which may be the same or different, covalently bonded by ester or amide bonds to the polymer. It was achieved by providing a sensor for determining the concentration of dissolved material in an aqueous medium.

The mixing of the polymer and the fluorescent organic substituent forms a fluorescent polymerizable indicator, examples of which are indicators for pO ₂ , pH and pCO ₂ .

U.S. Patent 5,262,037 discloses an electrochemical sensor that determines the partial pressure of oxygen in the blood stream. The electrochemical sensor for pO ₂ can be used with a pH sensor and a pCO ₂ sensor to form a multivariable sensor. In the multivariate sensor the pH sensor and the pCO ₂ sensor have a plurality of cells in which a portion of the sensor is in contact with the medium and the portion is arranged to substantially comprise a cutaway region of the wavelength guide, each of the cells being the analyte. It is prepared according to the specification of US Pat. No. 4,889,407, which provides an optical wavelength guide sensor for determining an analyte in a medium, including optical wavelength guide containing an indicator sensitive to the medium. Preferred wavelengthguides are optical fibers and the disclosed indicators include absorption indicators for pH, such as phenol red, and fluorescent indicators, such as pyrene butyric acid for 1β-umbelliferone and pO ₂ for pH or pCO ₂ . In the manufacture of the sensor, a portion of the fiber containing the cell is immersed in the indicator solution and the appropriate gel-forming component, and the impregnated fiber is evacuated so that the cell is evacuated so that the solution enters and the gel is cured so that the indicator is stable in the cell. Remaining in a manner, the indicator is attached to the cells of the optical fiber in the form of gels or solids.

PCT Patent Publication No. WO 91/05252 discloses a carbon dioxide monitor consisting of an indicator film material comprising an intrinsic mixture of a transparent polymer vehicle, and an indicator material that changes color upon exposure to carbon dioxide. Indicator materials include salts of indicator anions and lipophilic organic quaternary cations.

U.S. Patent 5,005,572 discloses a detector for determining carbon dioxide in a respiratory gas and a method for properly placing an intubation instrument in a patient's organ. Carbon dioxide detectors include a pH sensitive dye, a solid support and a migration enhancer to increase the reaction between H ₂ CO ₃ and pH sensitive dye.

US Pat. No. 4,728,299 discloses a transparent window incorporating an indicator component comprising a carrier fixedly attached to an indicator element comprising a color pH sensitivity indicator that changes color when the concentration of carbon dioxide in the ambient atmosphere exceeds 2%. A combination of rapid reactive mechanisms for detecting carbon dioxide in a gas mixture surrounded is disclosed. The instrument is used to determine the exact location of the endotracheal catheter.

The present invention relates to a solid state sensor. More specifically, the present invention relates to a stable solid state sensor used to determine the concentration of gases, in particular pH in liquid media such as human blood, in combination with pO ₂ and pCO ₂ and appropriate indicators.

The function and stability of the analytes in the medium, in particular the sensors for determining pO ₂ , pCO ₂ and pH in both liquid and gaseous media, are described in the appropriate indicators for use with the polymeric silicone carbinol as described later. Was found to increase significantly.

According to the present invention there is provided a stabilized substrate formed from a polymer which is a crosslinked solid silicone rubber formed from silicone carbinol having a molecular structure compatible with the indicator that is inert to the medium and analyte and does not affect the sensitivity of the indicator. Together there is provided a stable bio-inert sensor for determining the analyte in the medium, including chemical indicators sensitive to the analyte.

The polymerizable silicone rubber used in the sensor of the present invention is preferably one of two types:

1. Silicone carbinol homopolymers having the formula

Wherein R is methyl or phenyl, z is an integer from 1 to 20, n is an integer from 2 to 500;

2. Carbinol siloxane copolymers having the formula

Wherein R is methyl or phenyl, respectively, R is the same or different, z is an integer from 1 to 20, x and y are each an integer and the sum of x and y is 2 to 500.

Especially preferred homopolymers of Formula 1 are methyl silicone carbinol homopolymers having the formula

Wherein n is an integer from 2 to 500.

Preferred copolymers of formula (2) are dimethyl / methyl carbinol siloxane copolymers having formula (4):

Wherein x and y are each positive integers and the sum of x and y is 2 to 500.

The linear polymer has unique characteristics that can be attributed to carbinol side chains.

Carbinol as used herein is a generic term for silicones with different alkoxy side chains. Crosslinked carbinol groups form a hydrophobic gas permeable silicone matrix with an analyte sensitive indicator therein. Particularly preferred indicators are the oxygen sensitive ruthenium described below. Another preferred indicator is an indicator that detects carbon dioxide, such as phenol red.

The linear silicone polymers acting as substrates in the sensor according to the invention are preferably prepared by protecting the terminally unsaturated long chain alcohols and then in the hydrosilylation reaction (also referred to as hydrosilylation reaction) of the selected hydrosilicon. The final step is the deprotection of alcohol-OH groups.

Reactions with chemistry similar to the above reactions are known in the art. For example, hydrosilylation reactions are disclosed in US Pat. No. 3,122,522. However, prior to the present invention, the type of silicone polymer prepared following the mentioned reaction was not used as an indicator to sense analytes for making the unique sensor disclosed herein. In particular the advantage of the novel sensors of the present invention is the way in which the silicon carbinol is cross-linked to form a solid silicone rubbery polymer that can be processed to mix with different indicators to form the desired sensor.

Some of the unique benefits of the materials used in the sensors of the present invention

a) a long carbinol side chain that acts as a surfactant to dissolve water insoluble polar substances. In essence, they displace plasticizers in plasticized solid matrices that are the critical elements of currently available pO ₂ and pCO ₂ sensors. These dissolved side chains are particularly compatible with polar transition metal complexes which preferably contain nonpolar hydrocarbons and unsaturated hydrocarbon ligands.

b) The size and length of the carbinol side chain can vary depending on the shape of the crosslinked solid polymer. The same polymer can also be made less hydrophobic by reducing the carbon chain length and can be very hydrophilic (even water soluble) if z is 4 or less in formula (1) or (2). The hydrophilicity of the polymer can also be controlled by mixing long and short chain alcohol groups in the same linear prepolymer.

c) The stability of the silicone polymer and the prepolymer is greatly increased by the polysiloxane backbone. The polymers have high resistance to various chemicals and are preserved intact even after prolonged exposure to water vapor and biological gases. The stability under gamma radiation is comparable, although not better than PVA. Some conversion of free alcohol groups to ether bonds can occur by the formation of —O. And H. radicals.

d) The linear silicone prepolymer as well as the final polymer have no adverse effects and no exudation of the indicator element as shown in the preliminary cytotoxicity studies.

Particularly preferred embodiments of the invention are described below.

1. Polyurethane type curing system:

Silicon produced favorably by incorporating an alcohol polymer side chain as an oxygen sensing ruthenium indicator (ie, tris (4,7-diphenyl-1,10-phenanthroline) ruthenium (II) chloride) and a dissolution environment (for indicators) The rubber matrix is prepared as follows: The selected prepolymer (polysilicon linear polymer with alcohol side chains attached by silicon-carbon bonds) reacts with the difunctional isocyanate in the presence of a catalyst such that some alcohol groups are shown in the formula below. It forms a silicone matrix that is crosslinked by type linking.

The crosslinker may be any one of a number of diisocyanates commercially available.

Preferred catalysts are dibutyltindilaurate (DBTDL) having the formula [CH ₃ (CH ₂ ) ₃ ] ₂ Sn [O ₂ C (CH ₂ ) ₁₀ CH ₃ ] ₂ .

Low molecular weight silicone carbinol (carbinol in this and all other compounds below is understood to be C ₁₀ alcohol unless otherwise specified) is mixed with a ruthenium indicator already dissolved in methylene chloride; The two solutions are mixed and the mixture is purged with air to remove methylene chloride. The use of a solvent to predissolve the ruthenium indicator prior to addition to the silicone carbinol is merely to increase the convenience and speed of the mixing process. Alternatively, the indicator can be dissolved directly in the silicon carbinol (s) by sonication.

The clear magenta polymer precursor mixture is then mixed with the appropriate difunctional isocyanate and cured in an oven at 65 ° C. Cure times replace currently used isocyanates with more reactive aromatic isocyanates and / or more catalysts (i.e., tolylene diisocyanate or TDI with tin catalysts such as DBTDL will allow silicone carbinol to be 2 to 10 minutes at room temperature). It can be shortened by adding).

A typical polymer precursor mixture is 80 to 90% of silicone C ₁₀ -carbinol, prepolymer of 25 mg / g ruthenium indicator predissolved in methylene chloride and treated as disclosed above, 10 to 20% diisocyanate crosslinker, 0.01 To 2% catalyst (selective, accelerate curing) and ^* tris (4,7-diphenyl-1,10-phenanthroline) ruthenium (II) chloride.

A typical mixture for a thermal cure system is 900 mg low molecular weight silicone C ₁₀ -carbinol homopolymer, 25 g of Ru indicator (chloride) pre-dissolved in methylene chloride and mixed with silicon carbinol, 10% by weight ^* iso 100 mg of poron diisocyanate (IPDI), and 100 mL of 1% DBTDL catalyst in methylene chloride (actually 0.01% of total catalyst concentration).

^The polymer precursor + crosslinker is considered 100% of the total weight; The weight of the ruthenium indicator is not included and the weight of the catalyst is not considered part of the total weight unless it exceeds 1% of the total weight.

The working time of the mixture is from 60 to 90 minutes; This can be extended by the selection of suitable crosslinkers and catalysts.

2. Curing polyether type:

In this embodiment, it has surprisingly been found that certain silicone carbinols can be cured (forming solid silicone rubber) in the presence of a tin catalyst (DBTDL), possibly by alcohol side chains which reacted with each other to form ether bonds.

The solid has been made of a polymeric silicone carbinol homopolymer with tin catalyst at concentrations of up to 0.5% by weight. Low molecular weight silicone carbinol homopolymers failed to produce solids at low concentrations of DBTDL. When producing oxygen sensors in this way, the concentration of tin catalysts should be kept low (not exceeding 2%) to prevent other side reactions that may occur. The oxygen sensing ability of is lowered, which is presumed to be due to some redox occurring between the ruthenium (II) ions and the catalyst).

Low molecular weight silicon carbinol can be used to produce pCO ₂ sensors in the solid state in this manner.

3. Alcohol Protector (Delayed Curing System):

As a better control of the curing process and as an extension of this embodiment, it is desirable to have silicone carbinol (s) with blocked -OH groups, which, upon deprotection, can chemically react with the same type described above. The protecting groups can be used as chemical and thermal switches for the chosen polymerization process.

One such embodiment involves the use of trimethylsiloxy derivatives (TMS) which can be deprotected in situ to produce free -OH groups and initiate polymerization.

Low and medium molecular weight TMS-protected silicone carbinols (which are also intermediates for the preparation of corresponding carbinols) and hydrolyzed TMS groups are prepared by exposing the polymer precursor mixture to HCl vapor.

The reaction then proceeds as with Method 1 or Method 2 (or other type of curing comprising an alcohol —OH group).

The filled fiber sensor (made of polymethyl methacrylate, PMMA, fiber) can be placed in a closed chamber filled with hydrochloric acid gas or simply placed on top of a dish containing concentrated aged HCl. In this case, conditions that cure quickly (catalyzed TDI curing agent) are preferred to minimize the problems often encountered in long-term cure polymerization.

The only disadvantage of this approach is that once polymerization is initiated at the surface of the polymer mixture, further polymerization is controlled by the rate of hydrolysis of the TMS group (ie the rate of diffusion of HCl gas through the already formed polymer). The poly (methyl methacrylate) fibers themselves must be unaffected by exposure to HCl gas because their hydrolysis conditions are quite stringent (ie PMMA surface corrosion occurs in hot alcoholic KOH or concentrated sulfuric acid). The fiber coating consists of chemically inert perfluorinated hydrocarbons and therefore must remain intact.

Other alcohol protecting groups can be used as candidates for controlling the delayed curing process.

4. UV Curing System:

Several concepts used in thermal curing systems have been extended to silicone carbinol, which can be UV-cured. Partial substitution of an alcohol group with a methacrylate group provides a means of such a system; Linear chain extension and crosslinking occur with free radical mechanisms via methacrylate groups.

UV-initiators are benzoin iso-butyl ether or other benzoin derivatives commercially available.

Another approach is to partially esterify silicone carbinol-OH groups with methacrylic acid. The system has been tested with encouraging results. For example, a polydimethylsiloxane / methyl C ₁₀ -carbinol (37-40%) copolymer fully esterified with methacrylate groups is UV-irradiated in the presence of a liquid UV-initiator (benzoin iso-butyl ether) , Hard solids were produced. Under the same conditions, several low molecular weight silicone carbinols of low methacrylate content (less than 7.5%) produced gels or very soft solids.

Another method is partially with methacrylate groups, which can be UV-cured to become a gas permeable solid and still leave a sufficient number of free carbinol side chains to stabilize the ruthenium indicator and provide greater flexibility and elasticity to the cured polymer. Production of esterified low viscosity silicone C ₁₀ carbinol homopolymers. Crosslinking via carbon-carbon bonds generally produces solids that are more brittle when crosslinking occurs through urethane groups or polyether bond RORs. About 20% of the methacrylate groups on the carbinol homopolymer are generally sufficient to produce the solids and the remaining 80% of the free carbinol chains are left to soften the polymer.

The main disadvantage of this approach is the handling and storage of methacrylated silicones, which can have a short shelf life (these materials are prepolymerized unless stored away from low temperatures and sunlight). Another disadvantage is the inability to apply this type of chemistry to the production of solid state pCO ₂ sensors since any radicals produced upon exposure to UV-irradiation can destroy the pH indicator.

Some advantages of the process include the setting of automated processes and curing if desired. There may also be an additional advantage of mixing multiple curing methods on a single fiber by mixing the curing methods currently used in the manufacture of pH sensors and the manufacturing methods of pO ₂ sensors initiated with free radicals.

5. Photolabile protecting group Chemistry:

As a special case of alcohol protecting groups and in connection with the protecting groups disclosed in 3 and 4 above, the use of alcohol-OH protecting groups which can be photolysed by exposure to UV-irradiation has been particularly contemplated. Such groups have been used successfully in sugar chemistry and have been used in gene and DNA investigations.

In another embodiment, ortho-nitrobenzyl ether was selected as the main protecting group since benzyl groups and free alcohols were quantitatively hydrolyzed upon irradiation at 320 nm or more for 10 minutes. The reaction can be shown by the following scheme.

Wherein ROH is alcohol or sugar and X is chlorine or bromine.

The same type of chemistry can be extended to silicone carbinol. Thus, C ₁₀ -alcohols are alkylated with 2-nitrobenzyl bromide and the resulting nitrobenzyl ethers are hydrolyzed upon exposure to high concentrations of UV-irradiation (as apparent by -OH stretching vibrations in the infrared spectroscopy of the crude product).

Nitrobenzyl protected silicone carbinols are prepared directly by alkylation with 2-nitrobenzyl halide or by first alkylating unsaturated alcohols followed by hydrosilylation of the nitrobenzyl protected alcohols with hydrosilicon.

Prepolymer mixtures containing nitrobenzyl protected silicone carbinol ruthenium indicators, and TDI with tin catalyst can be UV irradiated when the sensor fibers are filled to fix the standards and a heat cured polyurethane solid is formed. .

The reaction can be prepared according to any of the above disclosed chemistries available.

The by-product ortho-nitrosobenzalaldehyde remains in the matrix but should not adversely affect polyurethane curing. Nitrate esters can also be used as alcohol protecting groups that can be photolyzed. Irradiation and subsequent decomposition thereof will produce only gaseous byproducts and will be more suitable for the production of the final polymer.

The following examples illustrate the preparation of indicator-polymer combinations of pO ₂ sensors according to the present invention.

[Brief Description of Drawings]

EXAMPLE

The desired concentration of oxygen sensing indicator in the final polymer matrix is 25 mg indicator / g. The polymer is made of 80% silicone carbinol and 20% IPDI (isophorone diisocyanate) crosslinker. A stock solution of indicator + silicon carbinol can be prepared and stored indefinitely. The preparation method of the stock solution is as follows.

1) Record the weight of the 16 x 125 mm test tube and appropriate receiving beaker.

2) 4 g of silicon carbinol was placed in a test tube.

3) In each beaker, 0.125 g ruthenium (chloride type) indicator was added to 1.25 cc of methylene chloride and completely dissolved.

4) The indicator solution was added to the silicone carbinol and mixed well. This was done by inhaling and pushing the mixture into a disposable pipette.

5) The air source was connected to a disposable tip of a 200 μl pipette. The tip of the pipette was placed in a test tube with a polymer / indicator mixture and air was blown through the mixture until all the methylene chlorides determined by weighing were blown off.

Then, 0.01% DBTDL (dibutyltin dilaurate) catalyst was prepared as follows:

1) 100 μl of dibutyltin dilaurate (DBTDL) was added to 10 ml of methylene chloride to prepare a 1% solution.

2) A 0.01% solution was prepared by adding 100 μl of 1% solution to 10 ml methylene chloride.

The final sensor was formed by filling a cell in an optical fiber made according to the method disclosed in US Pat. No. 4,889,407 as disclosed above. When the cell of the fiber optic sensor was ready to be filled, the polymer was prepared as follows.

1) Record the weight of a 10 x 75 mm test tube and a suitable receiving beaker.

2) 0.4 g stock solution (Si-carb + indicator) was placed in a test tube.

3) 1 cc of methylene chloride was added to the test tube and mixed well with a disposable pipette.

4) 0.1 g of IPDI was added to the test tube and mixed well as above with the same disposable pipette.

5) 500 μl of 0.01% DBTDL solution was added to the test tube and mixed well as above with the same disposable pipette.

6) The mixture was purged with air to remove methylene chloride. The mixture was weighed to determine when all methylene chloride was removed.

It took 20 to 30 minutes until all solvent was removed. After this time the mixture was pipetted into a cell of pO ₂ fibers for 60 to 90 minutes. At this time, the mixture becomes too thick to work. After the fiber is filled, the polymer is cured in an oven at 65 ° C. for 24 hours. In practice, curing can occur after two to three hours, but is reliably terminated within 24 hours.

The method disclosed in this embodiment can also be used for the manufacture of pCO ₂ sensors. In a preferred embodiment, the carbon dioxide sensing indicator is formed from an ionic complex of an lipophilic quaternary ammonium cation and an anion of sulfonphthalein dyes (eg, tetraoctylammonium hydroxide and phenol red). The indicator is incorporated into a silicone carbinol polymer matrix suitable for filling the cells of the optical fiber as disclosed above. The polymer / indicator matrix provides a system that responds quickly to changes in carbon dioxide concentration.

Multivariate sensors, including electrochemical sensors for determining pO ₂ as disclosed in US Pat. No. 5,262,037, in combination with pH and pCO ₂ sensors prepared as disclosed in US Pat. No. 4,889,407, are assignable to the present invention. It is currently manufactured by Biomedical Sensors Ltd. The technique of the present invention can be applied to an optical fiber structure as disclosed in US Pat. No. 4,889,407 to produce an optical fiber pO ₂ sensor capable of substituting the electrochemical pO ₂ sensor used in the aforementioned multivariable sensor. Likewise pCO ₂ and pH sensors can be made in accordance with the present invention, and the resulting multivariate sensor, which is similar in other respects to currently available sensors, has a number of advantages.

For example, in the manufacture of a pCO ₂ sensor according to the techniques disclosed in the prior art, films containing indicators are cast allowing the evaporation of a large amount of solvent. The casting technique does not facilitate filling of cells in the optical fiber due to volume loss due to solvent evaporation. In addition, the polymer used to form the film will not be very permeable to carbon dioxide and will provide a fast reaction only when the film is very thin and plastic. Another problem with the prior art is that the polymer and the plasticizers themselves are the source of acid or base, shifting the pH range of the sensor that reacts to pCO ₂ . In applications such as the determination of the exact position of the endotracheal tube, the latter problem is not of great importance since the film-based sensor is mainly used as color conversion. However, in a preferred embodiment of the invention, i.e. in a multivariate sensor incorporated into an insertion catheter for determining the concentration of the analyte in the blood of the patient, the color change is used as part of the analytical parameter system and the CO ₂ -sensing range of the matrix. Any change in the acid and / or base component of the polymer of the matrix, which will shift the will jeopardize the accuracy of the measurement by the sensor.

Although many known silicone rubbers have been investigated in an attempt to solve this problem, indicator composites have been found to inhibit the curing of all neutral cured silicones investigated. However, the problem was solved using the silicone carbinol polymer of the present invention. The polymers of the present invention provide a neutral matrix that has no volume loss during cure and has a permeation property similar to that of silicon, and the pCO ₂ sensor made therefrom provides a response to changes in CO ₂ concentration. More importantly, the curing of the system is not affected by the presence of the indicator complex.

Many pCO ₂ sensors made in accordance with the present invention and their performance are very good. Depending on the crosslinking, the 90% reaction time varies widely from 75 seconds to 360 seconds with a typical 55% modulation. This is good compared to current sensors with a modulation range of 25% to 55% and a response time of 150 seconds to 200 seconds.

In addition to use in multi-variable fiber optic sensors as disclosed herein above, by incorporation of a suitable substrate, a CO ₂ sensor made from a silicone carbinol polymer according to the present invention is a device similar to that disclosed in US Pat. No. 4,728,499. It can be used in an instrument for determining the position of the endotracheal tube in the trachea of a patient such as

For the pO ₂ sensors disclosed herein and illustrated in the examples, the preferred indicator tris (4,7-diphenyl-1,10-phenanthroline) ruthenium (II) chloride is in its preferred physical characteristics and oxygen sensing technology Used due to the history of the application. It has a high extinction coefficient for the two charge transfer bands seen in visible light spectroscopy. The excitation wavelength is compatible with current blue LEDs. The luminescence quantum yield is quite high (n ^- 0.5) and can sometimes be double (approximately integrated) when the indicator is incorporated into the polymer matrix. In addition to having strong visible light absorption, the indicator also has a strong fluorescence with a noticeable stoke shift of n ^- 140 nm. Thus, interference from reflected background light is minimal.

Both luminescence quantum yield and luminescence efficiency are independent of the excitation wavelength. The quenched oxygen quenching constant is quite high and increases the sensitivity to the subject (O ₂ ) analyte. Non-radioactive quench constants change in different media (solvents, polymers) but are not critical enough to overcome radioactive release.

Preferred indicators are also thermally, chemically and photochemically stable. Any long time light bleaching is minimal (especially commonly used low energy light sources) and this greatly increases the half life of the sensor. Tests using gamma-irradiation to sterilize show about 20-25% of indicator collapse, but this is favorable compared to the losses observed with other indicators.

It should be understood that other pO ₂ and pCO ₂ indicators can be used in the sensor according to the invention. For example, suitable indicators for pO ₂ crystals are platinum meso-tetra (penta fluorophenyl) porphine and platinum meso-tetraphenyl porphine; Suitable pCO ₂ indicators are cresol red and thymol blue.

Claims (8)

Substrates formed from polymers that are inert to the medium and analyte and do not affect the sensitivity of the indicator, wherein the polymer is a crosslinked solid silicone rubber made from silicone carbinol having a molecular structure compatible with the indicator. A stabilized bio-inert sensor for the determination of an analyte in a medium, comprising a chemical indicator that is sensitive to the analyte while stabilizing. The sensor of claim 1 wherein the polymer is a silicone carbinol homopolymer having the formula Wherein R is methyl or phenyl, z is an integer from 1 to 20 and n is an integer from 2 to 500. The sensor of claim 2, wherein the polymer is a methyl silicone carbinol homopolymer having Formula 3: Wherein n is an integer from 2 to 500. The sensor of claim 1 wherein the polymer is a carbinol siloxane copolymer having the formula Wherein R is each methyl or phenyl, R is the same or different, z is an integer from 1 to 20, x and y are each an integer and the sum of x and y is 2 to 500. The sensor of claim 4, wherein the copolymer of Formula 2 wherein the polymer is preferred is a dimethyl / methyl carbinol siloxane copolymer having Formula 4 above. Wherein x and y are each positive integers and the sum of x and y is 2 to 500. The sensor of claim 1, wherein the indicator is an oxygen-sensitive fluorescent indicator tris (4,7-diphenyl-1,10-phenanthroline) ruthenium (II) chloride. The sensor of claim 1, wherein the indicator is an ionic complex of an anionic of the lipophilic quaternary ammonium cation and the sulfonphthalein indicator. 8. The sensor of claim 7, wherein the indicator is an ionic complex of tetraoctylammonium hydroxide and phenol red.